title: Management and outcomes of major bleeding during treatment with dabigatran or warfarin.
abstract: BACKGROUND
  The aim of this study was to compare the management and prognosis of major bleeding in patients treated with dabigatran or warfarin.
  
  
  RESULTS
  Two independent investigators reviewed bleeding reports from 1034 individuals with 1121 major bleeds enrolled in 5 phase III trials comparing dabigatran with warfarin in 27 419 patients treated for 6 to 36 months. Patients with major bleeds on dabigatran (n=627 of 16 755) were older, had lower creatinine clearance, and more frequently used aspirin or non-steroid anti-inflammatory agents than those on warfarin (n=407 of 10 002). The 30-day mortality after the first major bleed tended to be lower in the dabigatran group (9.1%) than in the warfarin group (13.0%; pooled odds ratio, 0.68; 95% confidence interval, 0.46-1.01; P=0.057). After adjustment for sex, age, weight, renal function, and concomitant antithrombotic therapy, the pooled odds ratio for 30-day mortality with dabigatran versus warfarin was 0.66 (95% confidence interval, 0.44-1.00; P=0.051). Major bleeds in dabigatran patients were more frequently treated with blood transfusions (423/696, 61%) than bleeds in warfarin patients (175/425, 42%; P<0.001) but less frequently with plasma (dabigatran, 19.8%; warfarin, 30.2%; P<0.001). Patients who experienced a bleed had shorter stays in the intensive care unit if they had previously received dabigatran (mean 1.6 nights) compared with those who had received warfarin (mean 2.7 nights; P=0.01).
  
  
  CONCLUSIONS
  Patients who experienced major bleeding on dabigatran required more red cell transfusions but received less plasma, required a shorter stay in intensive care, and had a trend to lower mortality compared with those who had major bleeding on warfarin.
  
  
  BACKGROUND
  http://www.ClinicalTrials.gov. Unique identifiers: NCT00262600, NCT00291330, NCT00680186, NCT00329238 and NCT00558259.
authors.affiliation: Coagulation Unit, Hematology Center, Karolinska University Hospital and Karolinska Institute, Stockholm, Sweden (A.M., S.S.); the Department of Medicine, Soonchunhyang University Gumi's Hospital, North Kyungsang Province, South Korea (H.-G-H.); McMaster University, Population Health Research Institute, Hamilton, ON, Canada (S.J.C., J.W.E., S.Y.); Lankenau Medical Center, Thomas Jefferson Medical College, Wynnewood, PA (M.D.E.); Uppsala Clinical Research Center and Department of Medical Sciences, Uppsala University, Uppsala, Sweden (L.W.); Boehringer Ingelheim Pharma GmbH & Co KG, Ingelheim, Germany (M.B., M.F.); Faculty of Medicine Mannheim, University of Heidelberg, Mannheim, Germany (M.B.); and the Department of Medicine, McMaster University and Thrombosis and Atherosclerosis Research Institute, Hamilton, ON, Canada (S.S.).
authors.forename: Ammar
authors.initials: A
authors.lastname: Majeed
authors.forename: Hun-Gyu
authors.initials: HG
authors.lastname: Hwang
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Connolly
authors.forename: John W
authors.initials: JW
authors.lastname: Eikelboom
authors.forename: Michael D
authors.initials: MD
authors.lastname: Ezekowitz
authors.forename: Lars
authors.initials: L
authors.lastname: Wallentin
authors.forename: Martina
authors.initials: M
authors.lastname: Brueckmann
authors.forename: Mandy
authors.initials: M
authors.lastname: Fraessdorf
authors.forename: Salim
authors.initials: S
authors.lastname: Yusuf
authors.forename: Sam
authors.initials: S
authors.lastname: Schulman
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects; D000991:Antithrombins / Q000008:administration & dosage / Q000009:adverse effects; D001281:Atrial Fibrillation / Q000188:drug therapy* / Q000401:mortality; D001562:Benzimidazoles / Q000008:administration & dosage / Q000009:adverse effects*; D001803:Blood Transfusion / Q000706:statistics & numerical data; D000069604:Dabigatran; D005260:Female; D006454:Hemoglobins / Q000378:metabolism; D006470:Hemorrhage / Q000139:chemically induced* / Q000401:mortality / Q000628:therapy*; D006801:Humans; D007902:Length of Stay / Q000706:statistics & numerical data; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D016896:Treatment Outcome; D054556:Venous Thromboembolism / Q000188:drug therapy* / Q000401:mortality; D014859:Warfarin / Q000008:administration & dosage / Q000009:adverse effects*; D015091:beta-Alanine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*
chemical_list: D000925:Anticoagulants; D000991:Antithrombins; D001562:Benzimidazoles; D006454:Hemoglobins; D015091:beta-Alanine; D014859:Warfarin; D000069604:Dabigatran
keywords: anticoagulants; atrial fibrillation; hemorrhage; mortality; venous thrombosis